Development of organoids from human endometrial diseased tissues for mechanistic pathogenic research and (personalized) drug screening

Pros, cons & Future potential

• - Organoid models capture disease heterogeneity, maintain key features of the primary tissue, including the genetic background, and reproduce the lesion after in vivo transplantation.
• - Organoids show strong expandability thereby overcoming the hurdle of limiting quantities of primary biopsies.
• - Endometrial cancer-organoids show patient-specific drug responses, thereby providing conceptual evidence that the organoids are amenable to (personalized) drug screenings.
• - Organoids are state-of-the-art research models that bridge the gap between bench and bedside, more reliably than animal models do, and may thus in the future gradually substitute for the latter.

Typical organoids reproduce the epithelial compartment of a (diseased) tissue. Hence, more advanced models, also incorporating other cells (such as stromal, endothelial and immune cells), are still needed to fully replicate the original tissue.

Developing more complex organoid models containing the different cell types of a tissue.

• - The endometriosis organoid biobank can be valuable in deciphering disease (and type-specific) pathogenesis, especially if epithelial and stromal compartments are (re)combined in future studies, and in the search for drug targets that provide an alternative to current hormonal suppression therapy.
• - Organoids developed from hyperplastic endometrium (including Lynch syndrome) faithfully reproduce the disease genotype and can be valuable in the search for molecular mechanisms underlying the hyperplastic phenotype and its progression toward cancer.
• - Since organoids are typically composed of the epithelial compartment of the original tissue, further perfecting the model by adding stromal and immune components of the tumor/tissue microenvironment will eventually be needed to reach the organoid model's full potential.